Summary
Non‐digestible milk oligosaccharides were proposed as receptor decoys for pathogens and as nutrients for beneficial gut commensals like bifidobacteria. Bovine milk contains oligosaccharides, ...some of which are structurally identical or similar to those found in human milk. In a controlled, randomized double‐blinded clinical trial we tested the effect of feeding a formula supplemented with a mixture of bovine milk‐derived oligosaccharides (BMOS) generated from whey permeate, containing galacto‐oligosaccharides and 3'‐ and 6'‐sialyllactose, and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I‐3446. Breastfed infants served as reference group. Compared with a non‐supplemented control formula, the test formula showed a similar tolerability and supported a similar growth in healthy newborns followed for 12 weeks. The control, but not the test group, differed from the breast‐fed reference group by a higher faecal pH and a significantly higher diversity of the faecal microbiota. In the test group the probiotic B. lactis increased by 100‐fold in the stool and was detected in all supplemented infants. BMOS stimulated a marked shift to a bifidobacterium‐dominated faecal microbiota via increases in endogenous bifidobacteria (B. longum, B. breve, B. bifidum, B. pseudocatenulatum).
Summary
Some plant traits may be legacies of coevolution with extinct megafauna. One example is the convergent evolution of ‘divaricate’ cage architectures in many New Zealand lineages, interpreted ...as a response to recently extinct flightless avian browsers whose ancestors arrived during the Paleogene period. Although experiments have confirmed that divaricate habit deters extant browsers, its abundance on frosty, droughty sites appears consistent with an earlier interpretation as a response to cold, dry Plio‐Pleistocene climates.
We used 45 protein‐coding sequences from plastid genomes to reconstruct the evolutionary history of the divaricate habit in extant New Zealand lineages. Our dated phylogeny of 215 species included 91% of New Zealand eudicot divaricate species.
We show that 86% of extant divaricate plants diverged from non‐divaricate sisters within the last 5 Ma, implicating Plio‐Pleistocene climates in the proliferation of cage architectures in New Zealand.
Our results, combined with other recent findings, are consistent with the synthetic hypothesis that the browser‐deterrent effect of cage architectures was strongly selected only when Plio‐Pleistocene climatic constraints prevented woody plants from growing quickly out of reach of browsers. This is consistent with the abundance of cage architectures in other regions where plant growth is restricted by aridity or short frost‐free periods.
Fire is an important ecological disturbance in vegetated ecosystems across the globe, and also has considerable impacts on human infrastructure. Vegetation flammability is a key bottom-up control on ...fire regimes and on the nature of individual fires. Although New Zealand (NZ) historically had low fire frequencies, anthropogenic fires have considerably impacted indigenous vegetation as humans used fire extensively to clear forests. Few studies of vegetation flammability have been undertaken in NZ and only one has compared the flammability of indigenous plants; this was a qualitative assessment derived from expert opinion. We addressed this knowledge gap by measuring the flammability of terminal shoots from a range of trees and shrubs found in NZ. We quantified shoot flammability of 60 indigenous and exotic species, and compared our experimentally derived ranking with expert opinion. The most flammable species was the invasive exotic shrub Gorse (Ulex europaeus), followed by Manna Gum (Eucalyptus viminalis), Kūmarahou (Pomaderris kumeraho), Rimu (Dacrydium cupressinum) and Silver Beech (Lophozonia menziesii). Our experimentally derived ranking was strongly correlated with expert opinion, lending support to both methods. Our results are useful to ecologists seeking to understand how fires have and will influence NZ’s ecosystems, and for fire managers identifying high-risk landscapes, and low flammability species for ‘green firebreaks’.
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•Two new complexes of 2-DMAP and 4-DMAP with chloranilic acid were synthetized.•Location of the substituent (ortho and para) strongly influences crystal structure and pattern of the ...intramolecular hydrogen bond network.•Strong N+–H···O– hydrogen bonds are formed in the solid state.•Proton transfer is observed in both complexes in solid state but the ratio is 2:1 for 2-DMAP + CLA (ortho) and 1:1 for 4-DMAP + CLA (para).•Dynamics of methyl groups is different in 2-DMAP + CLA and 4-DMAP + CLA samples.
New complexes of 2-(N,N-dimethylamino)pyridine with chloranilic acid (2-DMAP + CLA) and 4-(N,N-dimethylamino)pyridine with chloranilic acid (4-DMAP + CLA) were synthesized and characterized by single crystal X-ray diffraction, infrared spectroscopy, thermal analysis methods and 1H, 13C and 15N NMR spectroscopy. The NMR spectroscopies were carried out in both, DMSO solution and in the solid state (CPMAS NMR). The 2-DMAP + CLA and 4-DMAP + CLA complexes crystallize in centrosymmetric P-1 and P21/c space group, respectively.
In both complexes, the phenomenon of proton transfer is observed, which results in the formation of strong N+–H···O– hydrogen bonds. Thermal decompositions of 2-DMAP + CLA and 4-DMAP + CLA complexes were studied by thermogravimetric analysis. Temperature dependent IR spectra revealed that methyl groups of 4-DMAP + CLA perform fast stochastic reorientational motion at room temperature which is slowed on cooling while in 2-DMAP + CLA reonrientational motion of CH3 groups is much slower due to steric effects.
Summary Non-digestible milk oligosaccharides were proposed as receptor decoys for pathogens and as nutrients for beneficial gut commensals like bifidobacteria. Bovine milk contains oligosaccharides, ...some of which are structurally identical or similar to those found in human milk. In a controlled, randomized double-blinded clinical trial we tested the effect of feeding a formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS) generated from whey permeate, containing galacto-oligosaccharides and 3'- and 6'-sialyllactose, and the probiotic Bifidobacterium animalis subsp. lactis (B.lactis) strain CNCM I-3446. Breastfed infants served as reference group. Compared with a non-supplemented control formula, the test formula showed a similar tolerability and supported a similar growth in healthy newborns followed for 12 weeks. The control, but not the test group, differed from the breast-fed reference group by a higher faecal pH and a significantly higher diversity of the faecal microbiota. In the test group the probiotic B.lactis increased by 100-fold in the stool and was detected in all supplemented infants. BMOS stimulated a marked shift to a bifidobacterium-dominated faecal microbiota via increases in endogenous bifidobacteria (B.longum, B.breve, B.bifidum, B.pseudocatenulatum).
The goal of this study was to develop a method for the simultaneous quantification of 23 commonly used antineoplastic drugs in a hospital pharmacy, using ultra-high pressure liquid chromatography ...separation coupled to tandem mass spectrometry detection (UHPLC-MS/MS). The following drugs were investigated: 5-fluorouracil, cytarabine, ganciclovir, gemcitabine, dacarbazine, methotrexate, pemetrexed, busulfan, topotecan, rentitrexed, ifosfamide, cyclophosphamide, etoposide, irinotecan, doxorubicin/epirubicin, vincristine, docetaxel, paclitaxel, daunorubicin, idarubicin, vinblastine, oxaliplatin and carboplatin. The chromatographic separation was performed on a phenyl-hexyl column (2.1 ×100 mm, 1.7 µm) with a gradient elution of methanol and water containing 10 mM ammonium formate adjusted to pH 4.9. All compounds were analyzed in less than 13 min and detected with a triple quadrupole mass spectrometer operating in MRM mode. Limits of detection (LODs) and limits of quantification (LOQs) were comprised between 0.01 and 5 ng.mL−1, and between 0.5 and 5 ng.mL−1, respectively. Accuracies ranged between 117% and 83% at the LOQ, intermediate and upper LOQ concentrations, with relative standard deviations (RSD) inferior to 8%, for all the antineoplastic drugs. Finally, the UHPLC-MS/MS method was successfully applied to the analysis of surface samples to evaluate the chemical contamination by these highly toxic compounds in a chemotherapy preparation unit in a hospital pharmacy with the purpose of monitoring the exposure of health care professionals.
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•A generic UHPLC-MS method was proposed for the analysis of antineoplastic drugs at trace level.•Complete separation of 23 antineoplastic drugs was achieved.•The UHPLC-MS method was successfully applied for wipe sample analysis.
Terrestrial plants and fire have interacted for at least 420 million years
. Whether recurrent fire drives plants to evolve higher flammability and what the evolutionary pattern of plant flammability ...is remain unclear
. Here, we show that phylogeny, the susceptibility of a habitat to have recurrent fires (that is, fire-proneness) and growth form are important predictors of the shoot flammability of 194 indigenous and introduced vascular plant species (Tracheophyta) from New Zealand. The phylogenetic signal of the flammability components and the variation in flammability among phylogenetic groups (families and higher taxonomic level clades) demonstrate that shoot flammability is phylogenetically conserved. Some closely related species, such as in Dracophyllum (Ericaceae), vary in flammability, indicating that flammability exhibits evolutionary flexibility. Species in fire-prone ecosystems tend to be more flammable than species from non-fire-prone ecosystems, suggesting that fire may have an important role in the evolution of plant flammability. Growth form also influenced flammability-forbs were less flammable than grasses, trees and shrubs; by contrast, grasses had higher biomass consumption by fire than other groups. The results show that shoot flammability of plants is largely correlated with phylogenetic relatedness, and high flammability may result in parallel evolution driven by environmental factors, such as fire regime.
•Presentation of the fingerprint methodology for the discrimination of manufacturing sources.•Collaborative study with seven European OMCLs working on the same samples with different analytical ...methods.•Selection of parameters and methods for the clustering of omeprazole samples according to their manufacturing sources.•Chemometric study on analytical data of 28 omeprazole API samples.•Benefit of data-fusion for fingerprint study.
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Like drug products, Active Pharmaceutical Ingredients (APIs) are subject to substandard and falsification issues, which represent a threat to patient health. In order to monitor the quality of drug substances and prevent the use of non-compliant APIs, Official Medicine Control Laboratories work together in a European network developing coordinated strategies and programmes. The API working group proposed a market surveillance study on omeprazole and omeprazole magnesium with the objectives of controlling the pharmaceutical quality of samples, checking compliance with the monographs of the European Pharmacopoeia, and collecting analytical fingerprints that could be further used to differentiate manufacturing sources for future authenticity investigations.
The study described in this article reports the analysis carried out by 7 European laboratories on 28 samples from 11 manufacturers with 5 analytical techniques (related substances with HPLC, residual solvents with GC-MS, near infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and X-ray powder diffractometry). The large amount of resulting analytical data were centralized and treated with two chemometric methods: Principal Component Analysis and Hierarchical Clustering Analysis. Data were analyzed separately and in combination (data fusion), allowing us to conclude that NMR and XRPD were suitable to differentiate samples originating from 9 out of 11 manufacturers. Analytical fingerprints associated with chemometrics were demonstrated to be a valuable methodology to discriminate manufacturers of omeprazole and omeprazole magnesium APIs and detect future substandard and falsified APIs.
Through its Active Pharmaceutical Ingredient Working Group (API-WG) the General European Official Medicines Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the ...Quality of Medicines & HealthCare (EDQM), regularly organises market surveillance studies for specific APIs for conformity to their monograph in the European Pharmacopoeia. During the past years some studies were combined with a fingerprint study of the APIs. The idea is to obtain a fingerprint for each manufacturer of the API under investigation, allowing the OMCL network to identify future samples as well as to detect substandard and falsified APIs.
This paper reports the results of the latest fingerprint study, organised on sildenafil citrate API samples. Seventy-nine samples from 14 different manufacturers were collected throughout the Network. Fingerprint data was collected through Mid-Infrared spectroscopy, Raman spectroscopy, liquid chromatography for related substances, gas chromatography for residual solvents, X-ray diffraction and Nuclear Magnetic Resonance (NMR) spectroscopy. Chemometrics applied to the collected data showed that all manufacturers could be discriminated based on the data of only three of these tests, i.e. gas chromatography for residual solvents, X-ray diffraction and proton NMR. Suspicious API samples for sildenafil citrate will therefore be analysed in the future with the selected techniques in order to link the sample to a manufacturer or demonstrate the absence of such link. If the sample cannot be attributed to one of the manufacturers, further analysis and research on provenance and identity will be required. Of course, if the suspected sample claims to originate from one of the manufacturers included in the study, analysis can be limited to the test distinguishing this manufacturer.
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•Related substances, residual solvents, 1H NMR, XRPD, FT-IR and Raman spectra were measured for 79 API samples.•Individual and combined techniques were used to discriminate the manufacturers.•The combination of residual solvents, 1H NMR and XRPD allows the discrimination between the manufacturers.•The test for residual solvents, 1H NMR and XRPD are the first choice to confirm authenticity or forgery.
Inelastic neutron scattering (INS) and infra-red (IR) spectroscopy methods were used for determination of dynamic structure of l-leucine – chloranilic acid complex. A theoretical dynamic pattern ...calculated by the density functional theory (DFT) method for periodic boundary conditions accompanied the experimental ones. Normal modes in the vibrational spectra were defined and described. The characteristic presence of the Hadži's trio enriched by numerous submaxima is observed in the wavenumber range 3200–800 cm−1. Bands assigned to CH3 torsion vibrations in the leucine cation were observed at 231 cm−1 and 258 cm−1 in the INS spectrum. Temperature-dependent far-infrared spectra in the temperature range 9 K–290 K were obtained. Vibrational bands were analyzed as a function of temperature. Activation energies for reorientational motion of CH3 and CH2 groups were determined by means of the band shape analysis performed for torsional and twisting vibrations of these groups. The estimated energy is equal to Ea = 2.7 ± 0.2 kJ/mol and Ea = 2.17 ± 0.12 kJ/mol for CH3 and CH2 groups, respectively. A phase transition at about 130 K in the l-leucine – chloranilic acid complex was observed.
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•l-Leucine - chloranilic acid complex was investigated by INS and temperature dependent IR spectroscopy.•DFT calculation for solids state model was performed.•The normal modes were described.•Activation energies for reorientational motion of the CH3 and CH2 groups were determined.•A phase transition about 130 K in the l-leucine – chloranilic acid complex was observed.
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